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Breast Cancer Metastasis

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Translational Research in Breast Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1187))

Abstract

Owing to increased awareness of the importance of mammogram and advances in surgical technology, survival rate of patients with primary breast cancer has dramatically increased. Despite all these advances in breast cancer treatment, there are no currently available treatments for this disease once it metastasizes to distant organs including bones, lungs, brain, and liver. This is mainly attributed to the complexity of metastatic process. Recent advances in technology enabled cancer biologists to dissect each step of the metastatic process, and this led to discovery of major players and molecules in this process. In this section, we will discuss recent discovery and advances in the field of breast cancer metastasis research.

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References

  1. Hofbauer LC, Rachner T, Singh SK. Fatal attraction: why breast cancer cells home to bone. Breast Cancer Res. 2008;10(1):101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Eichler AF, Chung E, Kodack DP, Loeffler JS, Fukumura D, Jain RK. The biology of brain metastases-translation to new therapies. Nat Rev Clin Oncol. 2011;8(6):344–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Disibio G, French SW. Metastatic patterns of cancers: results from a large autopsy study. Arch Pathol Lab Med. 2008;132(6):931–9.

    Article  PubMed  Google Scholar 

  4. Bos PD, Zhang XH, Nadal C, Shu W, Gomis RR, Nguyen DX, et al. Genes that mediate breast cancer metastasis to the brain. Nature. 2009;459(7249):1005–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, et al. Genes that mediate breast cancer metastasis to lung. Nature. 2005;436(7050):518–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kang Y, He W, Tulley S, Gupta GP, Serganova I, Chen CR, et al. Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. Proc Natl Acad Sci U S A. 2005;102(39):13909–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 2003;3(6):537–49.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang XH, Wang Q, Gerald W, Hudis CA, Norton L, Smid M, et al. Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell. 2009;16(1):67–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gupta GP, Nguyen DX, Chiang AC, Bos PD, Kim JY, Nadal C, et al. Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature. 2007;446(7137):765–70.

    Article  CAS  PubMed  Google Scholar 

  10. Bos PD, Nguyen DX, Massague J. Modeling metastasis in the mouse. Curr Opin Pharmacol. 2010;10(5):571–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lee JW, Komar CA, Bengsch F, Graham K, Beatty GL. Genetically engineered mouse models of pancreatic cancer: the KPC model (LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre), its variants, and their application in immuno-oncology drug discovery. Curr Protoc Pharmacol. 2016;73:14.39.1–14.39.20.

    Article  Google Scholar 

  12. Landis MD, Lehmann BD, Pietenpol JA, Chang JC. Patient-derived breast tumor xenografts facilitating personalized cancer therapy. Breast Cancer Res. 2013;15(1):201.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Marangoni E, Vincent-Salomon A, Auger N, Degeorges A, Assayag F, de Cremoux P, et al. A new model of patient tumor-derived breast cancer xenografts for preclinical assays. Clin Cancer Res. 2007;13(13):3989–98.

    Article  CAS  PubMed  Google Scholar 

  14. Lawson DA, Bhakta NR, Kessenbrock K, Prummel KD, Yu Y, Takai K, et al. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells. Nature. 2015;526(7571):131–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sinn E, Muller W, Pattengale P, Tepler I, Wallace R, Leder P. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell. 1987;49(4):465–75.

    Article  CAS  PubMed  Google Scholar 

  16. Henneman L, van Miltenburg MH, Michalak EM, Braumuller TM, Jaspers JE, Drenth AP, et al. Selective resistance to the PARP inhibitor olaparib in a mouse model for BRCA1-deficient metaplastic breast cancer. Proc Natl Acad Sci U S A. 2015;112(27):8409–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Dickins RA, McJunkin K, Hernando E, Premsrirut PK, Krizhanovsky V, Burgess DJ, et al. Tissue-specific and reversible RNA interference in transgenic mice. Nat Genet. 2007;39(7):914–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Premsrirut PK, Dow LE, Kim SY, Camiolo M, Malone CD, Miething C, et al. A rapid and scalable system for studying gene function in mice using conditional RNA interference. Cell. 2011;145(1):145–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sanchez-Rivera FJ, Jacks T. Applications of the CRISPR-Cas9 system in cancer biology. Nat Rev Cancer. 2015;15(7):387–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nieto MA. Epithelial plasticity: a common theme in embryonic and cancer cells. Science. 2013;342(6159):1234850.

    Article  PubMed  CAS  Google Scholar 

  21. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90.

    Article  CAS  PubMed  Google Scholar 

  22. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zheng H, Shen M, Zha YL, Li W, Wei Y, Blanco MA, et al. PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and metastasis. Cancer Cell. 2014;26(3):358–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 2011;20(5):576–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bill R, Christofori G. The relevance of EMT in breast cancer metastasis: correlation or causality? FEBS Lett. 2015;589(14):1577–87.

    Article  CAS  PubMed  Google Scholar 

  26. Gao D, Joshi N, Choi H, Ryu S, Hahn M, Catena R, et al. Myeloid progenitor cells in the premetastatic lung promote metastases by inducing mesenchymal to epithelial transition. Cancer Res. 2012;72(6):1384–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Clark AG, Vignjevic DM. Modes of cancer cell invasion and the role of the microenvironment. Curr Opin Cell Biol. 2015;36:13–22.

    Article  CAS  PubMed  Google Scholar 

  28. Lopez-Novoa JM, Nieto MA. Inflammation and EMT: an alliance towards organ fibrosis and cancer progression. EMBO Mol Med. 2009;1(6–7):303–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell. 2006;124(2):263–6.

    Article  CAS  PubMed  Google Scholar 

  30. Yang L, Huang J, Ren X, Gorska AE, Chytil A, Aakre M, et al. Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis. Cancer Cell. 2008;13(1):23–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Na YR, Yoon YN, Son DI, Seok SH. Cyclooxygenase-2 inhibition blocks M2 macrophage differentiation and suppresses metastasis in murine breast cancer model. PLoS One. 2013;8(5):e63451.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Su S, Liu Q, Chen J, Chen J, Chen F, He C, et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell. 2014;25(5):605–20.

    Article  PubMed  CAS  Google Scholar 

  33. Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3(6):453–8.

    Article  CAS  PubMed  Google Scholar 

  34. Weng D, Penzner JH, Song B, Koido S, Calderwood SK, Gong J. Metastasis is an early event in mouse mammary carcinomas and is associated with cells bearing stem cell markers. Breast Cancer Res. 2012;14(1):R18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Balic M, Lin H, Young L, Hawes D, Giuliano A, McNamara G, et al. Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res. 2006;12(19):5615–21.

    Article  CAS  PubMed  Google Scholar 

  36. Karaman S, Detmar M. Mechanisms of lymphatic metastasis. J Clin Invest. 2014;124(3):922–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. de Boer M, van Dijck JA, Bult P, Borm GF, Tjan-Heijnen VC. Breast cancer prognosis and occult lymph node metastases, isolated tumor cells, and micrometastases. J Natl Cancer Inst. 2010;102(6):410–25.

    Article  PubMed  Google Scholar 

  38. Roussos ET, Condeelis JS, Patsialou A. Chemotaxis in cancer. Nat Rev Cancer. 2011;11(8):573–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Keskin D, Kim J, Cooke VG, Wu CC, Sugimoto H, Gu C, et al. Targeting vascular pericytes in hypoxic tumors increases lung metastasis via angiopoietin-2. Cell Rep. 2015;10(7):1066–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Douma S, Van Laar T, Zevenhoven J, Meuwissen R, Van Garderen E, Peeper DS. Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature. 2004;430(7003):1034–9.

    Article  CAS  PubMed  Google Scholar 

  41. Kopp HG, Placke T, Salih HR. Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res. 2009;69(19):7775–83.

    Article  CAS  PubMed  Google Scholar 

  42. Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer. 2011;11(2):123–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ilie M, Hofman V, Long E, Bordone O, Selva E, Washetine K, et al. Current challenges for detection of circulating tumor cells and cell-free circulating nucleic acids, and their characterization in non-small cell lung carcinoma patients. What is the best blood substrate for personalized medicine? Ann Transl Med. 2014;2(11):107.

    PubMed  PubMed Central  Google Scholar 

  44. Racila E, Euhus D, Weiss AJ, Rao C, McConnell J, Terstappen LW, et al. Detection and characterization of carcinoma cells in the blood. Proc Natl Acad Sci U S A. 1998;95(8):4589–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Takao M, Takeda K. Enumeration, characterization, and collection of intact circulating tumor cells by cross contamination-free flow cytometry. Cytometry A. 2011;79(2):107–17.

    Article  PubMed  Google Scholar 

  46. Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10(20):6897–904.

    Article  PubMed  Google Scholar 

  47. Padua D, Zhang XH, Wang Q, Nadal C, Gerald WL, Gomis RR, et al. TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell. 2008;133(1):66–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Sevenich L, Bowman RL, Mason SD, Quail DF, Rapaport F, Elie BT, et al. Analysis of tumour- and stroma-supplied proteolytic networks reveals a brain-metastasis-promoting role for cathepsin S. Nat Cell Biol. 2014;16(9):876–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Qian B, Deng Y, Im JH, Muschel RJ, Zou Y, Li J, et al. A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS One. 2009;4(8):e6562.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 2011;475(7355):222–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gupta GP, Perk J, Acharyya S, de Candia P, Mittal V, Todorova-Manova K, et al. ID genes mediate tumor reinitiation during breast cancer lung metastasis. Proc Natl Acad Sci U S A. 2007;104(49):19506–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Chen Q, Zhang XH, Massague J. Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs. Cancer Cell. 2011;20(4):538–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Korpal M, Ell BJ, Buffa FM, Ibrahim T, Blanco MA, Celia-Terrassa T, et al. Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med. 2011;17(9):1101–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Malanchi I, Santamaria-Martinez A, Susanto E, Peng H, Lehr HA, Delaloye JF, et al. Interactions between cancer stem cells and their niche govern metastatic colonization. Nature. 2011;481(7379):85–9.

    Article  PubMed  CAS  Google Scholar 

  55. Oskarsson T, Acharyya S, Zhang XH, Vanharanta S, Tavazoie SF, Morris PG, et al. Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med. 2011;17(7):867–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Acharyya S, Oskarsson T, Vanharanta S, Malladi S, Kim J, Morris PG, et al. A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell. 2012;150(1):165–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Gao H, Chakraborty G, Lee-Lim AP, Mo Q, Decker M, Vonica A, et al. The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell. 2012;150(4):764–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Valiente M, Obenauf AC, Jin X, Chen Q, Zhang XH, Lee DJ, et al. Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell. 2014;156(5):1002–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Xing F, Kobayashi A, Okuda H, Watabe M, Pai SK, Pandey PR, et al. Reactive astrocytes promote the metastatic growth of breast cancer stem-like cells by activating Notch signalling in brain. EMBO Mol Med. 2013;5(3):384–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zhang L, Zhang S, Yao J, Lowery FJ, Zhang Q, Huang WC, et al. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature. 2015;527(7576):100–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Chen Q, Boire A, Jin X, Valiente M, Er EE, Lopez-Soto A, et al. Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature. 2016;533(7604):493–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Xu J, Xu Z, Zhou JY, Zhuang Z, Wang E, Boerner J, et al. Regulation of the Src-PP2A interaction in tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. J Biol Chem. 2013;288(46):33263–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Guise TA, Mohammad KS, Clines G, Stebbins EG, Wong DH, Higgins LS, et al. Basic mechanisms responsible for osteolytic and osteoblastic bone metastases. Clin Cancer Res. 2006;12(20 Pt 2):6213s–6s.

    Article  CAS  PubMed  Google Scholar 

  64. Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem. 2010;285(33):25103–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Jones DH, Nakashima T, Sanchez OH, Kozieradzki I, Komarova SV, Sarosi I, et al. Regulation of cancer cell migration and bone metastasis by RANKL. Nature. 2006;440(7084):692–6.

    Article  CAS  PubMed  Google Scholar 

  66. Obenauf AC, Massague J. Surviving at a distance: organ-specific metastasis. Trends Cancer. 2015;1(1):76–91.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Sethi N, Dai X, Winter CG, Kang Y. Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell. 2011;19(2):192–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lu X, Mu E, Wei Y, Riethdorf S, Yang Q, Yuan M, et al. VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging alpha4beta1-positive osteoclast progenitors. Cancer Cell. 2011;20(6):701–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ell B, Mercatali L, Ibrahim T, Campbell N, Schwarzenbach H, Pantel K, et al. Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic bone metastasis. Cancer Cell. 2013;24(4):542–56.

    Article  CAS  PubMed  Google Scholar 

  70. Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016;30(5):668–81.

    Article  CAS  PubMed  Google Scholar 

  71. Peinado H, Zhang H, Matei IR, Costa-Silva B, Hoshino A, Rodrigues G, et al. Pre-metastatic niches: organ-specific homes for metastases. Nat Rev Cancer. 2017;17(5):302–17.

    Article  CAS  PubMed  Google Scholar 

  72. Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438(7069):820–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989;8(2):98–101.

    CAS  PubMed  Google Scholar 

  74. Deng J, Liu Y, Lee H, Herrmann A, Zhang W, Zhang C, et al. S1PR1-STAT3 signaling is crucial for myeloid cell colonization at future metastatic sites. Cancer Cell. 2012;21(5):642–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Chafe SC, Lou Y, Sceneay J, Vallejo M, Hamilton MJ, McDonald PC, et al. Carbonic anhydrase IX promotes myeloid-derived suppressor cell mobilization and establishment of a metastatic niche by stimulating G-CSF production. Cancer Res. 2015;75(6):996–1008.

    Article  CAS  PubMed  Google Scholar 

  76. Peinado H, Lavotshkin S, Lyden D. The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts. Semin Cancer Biol. 2011;21(2):139–46.

    Article  CAS  PubMed  Google Scholar 

  77. Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, et al. The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol. 2008;10(11):1349–55.

    Article  CAS  PubMed  Google Scholar 

  78. Fremder E, Munster M, Aharon A, Miller V, Gingis-Velitski S, Voloshin T, et al. Tumor-derived microparticles induce bone marrow-derived cell mobilization and tumor homing: a process regulated by osteopontin. Int J Cancer. 2014;135(2):270–81.

    Article  CAS  PubMed  Google Scholar 

  79. Joo YN, Jin H, Eun SY, Park SW, Chang KC, Kim HJ. P2Y2R activation by nucleotides released from the highly metastatic breast cancer cell MDA-MB-231 contributes to pre-metastatic niche formation by mediating lysyl oxidase secretion, collagen crosslinking, and monocyte recruitment. Oncotarget. 2014;5(19):9322–34.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Erler JT, Bennewith KL, Cox TR, Lang G, Bird D, Koong A, et al. Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell. 2009;15(1):35–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Liu Y, Gu Y, Han Y, Zhang Q, Jiang Z, Zhang X, et al. Tumor exosomal RNAs promote lung pre-metastatic niche formation by activating alveolar epithelial TLR3 to recruit neutrophils. Cancer Cell. 2016;30(2):243–56.

    Article  PubMed  CAS  Google Scholar 

  82. Gil-Bernabe AM, Ferjancic S, Tlalka M, Zhao L, Allen PD, Im JH, et al. Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice. Blood. 2012;119(13):3164–75.

    Article  CAS  PubMed  Google Scholar 

  83. Kowanetz M, Wu X, Lee J, Tan M, Hagenbeek T, Qu X, et al. Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes. Proc Natl Acad Sci U S A. 2010;107(50):21248–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Wu CF, Andzinski L, Kasnitz N, Kroger A, Klawonn F, Lienenklaus S, et al. The lack of type I interferon induces neutrophil-mediated pre-metastatic niche formation in the mouse lung. Int J Cancer. 2015;137(4):837–47.

    Article  CAS  PubMed  Google Scholar 

  85. Zhao E, Wang L, Dai J, Kryczek I, Wei S, Vatan L, et al. Regulatory T cells in the bone marrow microenvironment in patients with prostate cancer. Onco Targets Ther. 2012;1(2):152–61.

    CAS  Google Scholar 

  86. Giles AJ, Reid CM, Evans JD, Murgai M, Vicioso Y, Highfill SL, et al. Activation of hematopoietic stem/progenitor cells promotes immunosuppression within the pre-metastatic niche. Cancer Res. 2016;76(6):1335–47.

    Article  CAS  PubMed  Google Scholar 

  87. Yamamura Y, Asai N, Enomoto A, Kato T, Mii S, Kondo Y, et al. Akt-Girdin signaling in cancer-associated fibroblasts contributes to tumor progression. Cancer Res. 2015;75(5):813–23.

    Article  CAS  PubMed  Google Scholar 

  88. Chin AR, Wang SE. Cancer tills the premetastatic field: mechanistic basis and clinical implications. Clin Cancer Res. 2016;22(15):3725–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Sceneay J, Chow MT, Chen A, Halse HM, Wong CS, Andrews DM, et al. Primary tumor hypoxia recruits CD11b+/Ly6Cmed/Ly6G+ immune suppressor cells and compromises NK cell cytotoxicity in the premetastatic niche. Cancer Res. 2012;72(16):3906–11.

    Article  CAS  PubMed  Google Scholar 

  90. Baumann M, Krause M, Hill R. Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer. 2008;8(7):545–54.

    Article  CAS  PubMed  Google Scholar 

  91. Prieto-Vila M, Takahashi RU, Usuba W, Kohama I, Ochiya T. Drug resistance driven by cancer stem cells and their niche. Int J Mol Sci. 2017;18(12):2574.

    Article  PubMed Central  CAS  Google Scholar 

  92. Chen D, Bhat-Nakshatri P, Goswami C, Badve S, Nakshatri H. ANTXR1, a stem cell-enriched functional biomarker, connects collagen signaling to cancer stem-like cells and metastasis in breast cancer. Cancer Res. 2013;73(18):5821–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100(7):3983–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1(5):555–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Oskarsson T, Batlle E, Massague J. Metastatic stem cells: sources, niches, and vital pathways. Cell Stem Cell. 2014;14(3):306–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Liao WT, Ye YP, Deng YJ, Bian XW, Ding YQ. Metastatic cancer stem cells: from the concept to therapeutics. Am J Stem Cells. 2014;3(2):46–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Liu H, Patel MR, Prescher JA, Patsialou A, Qian D, Lin J, et al. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Proc Natl Acad Sci U S A. 2010;107(42):18115–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V, et al. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol. 2013;31(6):539–44.

    Article  CAS  PubMed  Google Scholar 

  99. Bartucci M, Dattilo R, Moriconi C, Pagliuca A, Mottolese M, Federici G, et al. TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells. Oncogene. 2015;34(6):681–90.

    Article  CAS  PubMed  Google Scholar 

  100. Scheel C, Eaton EN, Li SH, Chaffer CL, Reinhardt F, Kah KJ, et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell. 2011;145(6):926–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Oft M, Peli J, Rudaz C, Schwarz H, Beug H, Reichmann E. TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev. 1996;10(19):2462–77.

    Article  CAS  PubMed  Google Scholar 

  102. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Xing Z, Lin A, Li C, Liang K, Wang S, Liu Y, et al. lncRNA directs cooperative epigenetic regulation downstream of chemokine signals. Cell. 2014;159(5):1110–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Liu B, Sun L, Liu Q, Gong C, Yao Y, Lv X, et al. A cytoplasmic NF-kappaB interacting long noncoding RNA blocks IkappaB phosphorylation and suppresses breast cancer metastasis. Cancer Cell. 2015;27(3):370–81.

    Article  CAS  PubMed  Google Scholar 

  105. Li C, Wang S, Xing Z, Lin A, Liang K, Song J, et al. A ROR1-HER3-lncRNA signalling axis modulates the Hippo-YAP pathway to regulate bone metastasis. Nat Cell Biol. 2017;19(2):106–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Wang S, Liang K, Hu Q, Li P, Song J, Yang Y, et al. JAK2-binding long noncoding RNA promotes breast cancer brain metastasis. J Clin Invest. 2017;127(12):4498–515.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Kuang DM, Zhao Q, Peng C, Xu J, Zhang JP, Wu C, et al. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J Exp Med. 2009;206(6):1327–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009;16(3):183–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Sawant A, Hensel JA, Chanda D, Harris BA, Siegal GP, Maheshwari A, et al. Depletion of plasmacytoid dendritic cells inhibits tumor growth and prevents bone metastasis of breast cancer cells. J Immunol. 2012;189(9):4258–65.

    Article  CAS  PubMed  Google Scholar 

  110. Yang P, Li QJ, Feng Y, Zhang Y, Markowitz GJ, Ning S, et al. TGF-beta-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma. Cancer Cell. 2012;22(3):291–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Karavitis J, Hix LM, Shi YH, Schultz RF, Khazaie K, Zhang M. Regulation of COX2 expression in mouse mammary tumor cells controls bone metastasis and PGE2-induction of regulatory T cell migration. PLoS One. 2012;7(9):e46342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Dalotto-Moreno T, Croci DO, Cerliani JP, Martinez-Allo VC, Dergan-Dylon S, Mendez-Huergo SP, et al. Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease. Cancer Res. 2013;73(3):1107–17.

    Article  CAS  PubMed  Google Scholar 

  113. Novitskiy SV, Pickup MW, Gorska AE, Owens P, Chytil A, Aakre M, et al. TGF-beta receptor II loss promotes mammary carcinoma progression by Th17 dependent mechanisms. Cancer Discov. 2011;1(5):430–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Olkhanud PB, Damdinsuren B, Bodogai M, Gress RE, Sen R, Wejksza K, et al. Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4(+) T cells to T-regulatory cells. Cancer Res. 2011;71(10):3505–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus Docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Valsecchi ME. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(13):1270.

    Article  PubMed  Google Scholar 

  118. Katz H, Alsharedi M. Immunotherapy in triple-negative breast cancer. Med Oncol. 2017;35(1):13.

    Article  PubMed  CAS  Google Scholar 

  119. Song KH, Park MS, Nandu TS, Gadad S, Kim SC, Kim MY. GALNT14 promotes lung-specific breast cancer metastasis by modulating self-renewal and interaction with the lung microenvironment. Nat Commun. 2016;7:13796.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Li CW, Lim SO, Chung EM, Kim YS, Park AH, Yao J, et al. Eradication of triple-negative breast cancer cells by targeting glycosylated PD-L1. Cancer Cell. 2018;33(2):187–201.e10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Swierczak A, Cook AD, Lenzo JC, Restall CM, Doherty JP, Anderson RL, et al. The promotion of breast cancer metastasis caused by inhibition of CSF-1R/CSF-1 signaling is blocked by targeting the G-CSF receptor. Cancer Immunol Res. 2014;2(8):765–76.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea

    Mi Young Kim

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Correspondence to Mi Young Kim .

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  1. Department of Surgery, College of Medicine, Seoul National University, Seoul, Korea (Republic of)

    Dong-Young Noh

  2. College of Medicine, Seoul National University College of Medicine, Seoul, Korea (Republic of)

    Wonshik Han

  3. Graduate School of Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Masakazu Toi

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Kim, M.Y. (2021). Breast Cancer Metastasis. In: Noh, DY., Han, W., Toi, M. (eds) Translational Research in Breast Cancer. Advances in Experimental Medicine and Biology, vol 1187. Springer, Singapore. https://doi.org/10.1007/978-981-32-9620-6_9

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